tbuckley/cabot-search huggingface dataset:
Patient profiles in heart failure with reduced ejection fraction: Prevalence, characteristics, treatments and outcomes in a real‐world heart failure population
Authors: Francesca Musella, Giuseppe M.C. Rosano, Camilla Hage, Lina Benson, Federica Guidetti, Brenda Moura, Gerolamo Sibilio, Marco Boccalatte, Ulf Dahlström, Andrew J.S. Coats, Lars H. Lund, Gianluigi Savarese
Journal: European Journal of Heart Failure (2023)

The Heart Failure Association of the European Society of Cardiology has recently proposed to optimize guideline-directed medical treatments according to patient's profiles. The aim of this analysis was to investigate prevalence/characteristics/treatments/outcomes for individual profiles.Patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Swedish Heart Failure Registry (SwedeHF) between 2013 and 2021 were considered. Among 108 profiles generated by combining different strata of renal function (by estimated glomerular filtration rate [eGFR]), systolic blood pressure (sBP), heart rate, atrial fibrillation (AF) status and presence of hyperkalaemia, 93 were identified in our cohort. Event rates for a composite of cardiovascular (CV) mortality or first HF hospitalization were calculated for each profile. The nine most frequent profiles accounting for 70.5% of the population had eGFR 30-60 or ≥60 ml/min/1.73 m2 , sBP 90-140 mmHg and no hyperkalaemia. Heart rate and AF were evenly distributed. The highest risk of CV mortality/first HF hospitalization was observed in those with concomitant eGFR 30-60 ml/min/1.73 m2 and AF. We also identified nine profiles with the highest event rates, representing only 5% of the study population, characterized by no hyperkalaemia, even distribution among the sBP strata, predominance of eGFR <30 ml/min/1.73 m2 and AF. The three profiles with eGFR 30-60 ml/min/1.73 m2 also showed sBP <90 mmHg.In a real-world cohort, most patients fit in a few easily identifiable profiles; the nine profiles at highest risk of mortality/morbidity accounted for only 5% of the population. Our data might contribute to identifying profile-tailored approaches to guide drug implementation and follow-up.
Prevalence, characteristics and prognostic impact of aortic valve disease in patients with heart failure and reduced, mildly reduced, and preserved ejection fraction: An analysis of the ESC Heart Failure Long‐Term Registry
Authors: Bahira Shahim, Angiza Shahim, Marianna Adamo, Ovidiu Chioncel, Lina Benson, Maria G. Crespo‐Leiro, Stefan D. Anker, Andrew J.S. Coats, Gerasimos Filippatos, Mitja Lainscak, Theresa McDonagh, Alexandre Mebazaa, Massimo F. Piepoli, Giuseppe M.C. Rosano, Frank Ruschitzka, Gianluigi Savarese, Petar Seferovic, Maurizio Volterrani, Marisa Crespo Leiro, Javier Segovia Cubero, Offer Amir, Benjamin Palic, Aldo P. Maggioni, Marco Metra, Lars H. Lund
Journal: European Journal of Heart Failure (2023)

To assess the prevalence, clinical characteristics, and outcomes of patients with heart failure (HF) with or without moderate to severe aortic valve disease (AVD) (aortic stenosis [AS], aortic regurgitation [AR], mixed AVD [MAVD]).
Comparison of Left Bundle Branch Area Pacing and Biventricular Pacing in Candidates for Resynchronization Therapy
Authors: Pugazhendhi Vijayaraman, Parikshit S. Sharma, Óscar Cano, Shunmuga Sundaram Ponnusamy, Bengt Herweg, Francesco Zanon, Marek Jastrzebski, Jiangang Zou, Mihail G. Chelu, Kevin Vernooy, Zachary I. Whinnett, Girish M. Nair, Manuel Molina-Lerma, Karol Curila, Dipen Zalavadia, Abdul Haseeb, Cicely Dye, Sharath C. Vipparthy, Ryan Brunetti, Pawel Moskal, Alexandra Ross, Antonius van Stipdonk, Jerin George, Yusuf K. Qadeer, Mishal Mumtaz, Jeffrey Kolominsky, Syeda A. Zahra, Mehrdad Golian, Lina Marcantoni, Faiz A. Subzposh, Kenneth A. Ellenbogen
Journal: Journal of the American College of Cardiology (2023)
Current research trends of nanomedicines
Authors: Qiuyue Liu, Jiahui Zou, Zhongjian Chen, Wei He, Wei Wu
Journal: Acta Pharmaceutica Sinica B (2023)

Owing to the inherent shortcomings of traditional therapeutic drugs in terms of inadequate therapeutic efficacy and toxicity in clinical treatment, nanomedicine designs have received widespread attention with significantly improved efficacy and reduced non-target side effects. Nanomedicines hold tremendous theranostic potential for treating, monitoring, diagnosing, and controlling various diseases and are attracting an unfathomable amount of input of research resources. Against the backdrop of an exponentially growing number of publications, it is imperative to help the audience get a panorama image of the research activities in the field of nanomedicines. Herein, this review elaborates on the development trends of nanomedicines, emerging nanocarriers, in vivo fate and safety of nanomedicines, and their extensive applications. Moreover, the potential challenges and the obstacles hindering the clinical translation of nanomedicines are also discussed. The elaboration on various aspects of the research trends of nanomedicines may help enlighten the readers and set the route for future endeavors.
Long-Term Balancing Selection and the Genetic Load Linked to the Self-Incompatibility Locus in <i>Arabidopsis halleri</i> and <i>A. lyrata</i>
Authors: Audrey Le Veve, Nicolas Burghgraeve, Mathieu Genete, Christelle Lepers-Blassiau, Margarita Takou, Juliette De Meaux, Barbara K Mable, Eléonore Durand, Xavier Vekemans, Vincent Castric
Journal: Molecular Biology and Evolution (2023)

Abstract Balancing selection is a form of natural selection maintaining diversity at the sites it targets and at linked nucleotide sites. Due to selection favoring heterozygosity, it has the potential to facilitate the accumulation of a “sheltered” load of tightly linked recessive deleterious mutations. However, precisely evaluating the extent of these effects has remained challenging. Taking advantage of plant self-incompatibility as one of the best-understood examples of long-term balancing selection, we provide a highly resolved picture of the genomic extent of balancing selection on the sheltered genetic load. We used targeted genome resequencing to reveal polymorphism of the genomic region flanking the self-incompatibility locus in three sample sets in each of the two closely related plant species Arabidopsis halleri and Arabidopsis lyrata, and used 100 control regions from throughout the genome to factor out differences in demographic histories and/or sample structure. Nucleotide polymorphism increased strongly around the S-locus in all sample sets, but only over a limited genomic region, as it became indistinguishable from the genomic background beyond the first 25–30 kb. Genes in this chromosomal interval exhibited no excess of mutations at 0-fold degenerated sites relative to putatively neutral sites, hence revealing no detectable weakening of the efficacy of purifying selection even for these most tightly linked genes. Overall, our results are consistent with the predictions of a narrow genomic influence of linkage to the S-locus and clarify how natural selection in one genomic region affects the evolution of the adjacent genomic regions.
A <i>Caenorhabditis elegans</i> Male Pheromone Feminizes Germline Gene Expression in Hermaphrodites and Imposes Life-History Costs
Authors: David Angeles-Albores, Erin Z Aprison, Svetlana Dzitoyeva, Ilya Ruvinsky
Journal: Molecular Biology and Evolution (2023)

Abstract Sex pheromones not only improve the reproductive success of the recipients, but also impose costs, such as a reduced life span. The underlying mechanisms largely remain to be elucidated. Here, we show that even a brief exposure to physiological amounts of the dominant Caenorhabditis elegans male pheromone, ascr#10, alters the expression of thousands of genes in hermaphrodites. The most dramatic effect on the transcriptome is the upregulation of genes expressed during oogenesis and the downregulation of genes associated with male gametogenesis. This result reveals a way in which social signals help to resolve the inherent conflict between spermatogenesis and oogenesis in a simultaneous hermaphrodite, presumably to optimally align reproductive function with the presence of potential mating partners. We also found that exposure to ascr#10 increased the risk of persistent intestinal infections in hermaphrodites due to pathological pharyngeal hypertrophy. Thus, our study reveals ways in which the male pheromone can not only have beneficial effects on the recipients’ reproduction, but also cause harmful consequences that reduce life span.
Airway-Occluding Mucus Plugs and Mortality in Patients With Chronic Obstructive Pulmonary Disease
Authors: Alejandro A. Diaz, José L. Orejas, Scott Grumley, Hrudaya P. Nath, Wei Wang, Wojciech R. Dolliver, Andrew Yen, Seth J. Kligerman, Kathleen Jacobs, Padma P. Manapragada, Mostafa Abozeed, Muhammad Usman Aziz, Mohd Zahid, Asmaa N. Ahmed, Nina L. Terry, Ruben San José Estépar, Victor Kim, Barry J. Make, MeiLan K. Han, Sushilkumar Sonavane, George R. Washko, Michael Cho, Raúl San José Estépar
Journal: JAMA (2023)

Airway mucus plugs are common in patients with chronic obstructive pulmonary disease (COPD); however, the association of airway mucus plugging and mortality in patients with COPD is unknown.To determine whether airway mucus plugs identified on chest computed tomography (CT) were associated with increased all-cause mortality.Observational retrospective analysis of prospectively collected data of patients with a diagnosis of COPD in the Genetic Epidemiology of COPD cohort. Participants were non-Hispanic Black or White individuals, aged 45 to 80 years, who smoked at least 10 pack-years. Participants were enrolled at 21 centers across the US between November 2007 and April 2011 and were followed up through August 31, 2022.Mucus plugs that completely occluded airways on chest CT scans, identified in medium- to large-sized airways (ie, approximately 2- to 10-mm lumen diameter) and categorized as affecting 0, 1 to 2, or 3 or more lung segments.The primary outcome was all-cause mortality, assessed with proportional hazard regression analysis. Models were adjusted for age, sex, race and ethnicity, body mass index, pack-years smoked, current smoking status, forced expiratory volume in the first second of expiration, and CT measures of emphysema and airway disease.Among the 4483 participants with COPD, 4363 were included in the primary analysis (median age, 63 years [IQR, 57-70 years]; 44% were women). A total of 2585 (59.3%), 953 (21.8%), and 825 (18.9%) participants had mucus plugs in 0, 1 to 2, and 3 or more lung segments, respectively. During a median 9.5-year follow-up, 1769 participants (40.6%) died. The mortality rates were 34.0% (95% CI, 32.2%-35.8%), 46.7% (95% CI, 43.5%-49.9%), and 54.1% (95% CI, 50.7%-57.4%) in participants who had mucus plugs in 0, 1 to 2, and 3 or more lung segments, respectively. The presence of mucus plugs in 1 to 2 vs 0 and 3 or more vs 0 lung segments was associated with an adjusted hazard ratio of death of 1.15 (95% CI, 1.02-1.29) and 1.24 (95% CI, 1.10-1.41), respectively.In participants with COPD, the presence of mucus plugs that obstructed medium- to large-sized airways was associated with higher all-cause mortality compared with patients without mucus plugging on chest CT scans.
Lancet Commission on synergies between universal health coverage, health security, and health promotion
Authors: Irene Agyepong, Neil Spicer, Gorik Ooms, Albrecht Jahn, Till Bärnighausen, Claudia Beiersmann, Hannah Brown Amoakoh, Günter Fink, Yan Guo, Lisa Hennig, Mahlet Kifle Habtemariam, Bocar A Kouyaté, Rene Loewenson, Angela Micah, Suerie Moon, Mosa Moshabela, Sonja Lynn Myhre, Trygve Ottersen, Walaiporn Patcharanarumol, Malabika Sarker, Gita Sen, Yasuhisa Shiozaki, Francisco Songane, Devi Sridhar, Freddie Ssengooba, Jeanette Vega, Deisy Ventura, Maike Voss, David Heymann
Journal: The Lancet (2023)
Design and Baseline Characteristics of STEP-HFpEF Program Evaluating Semaglutide in Patients With Obesity HFpEF Phenotype
Authors: Mikhail N. Kosiborod, Steen Z. Abildstrøm, Barry A. Borlaug, Javed Butler, Louise Christensen, Melanie Davies, Kees G. Hovingh, Dalane W. Kitzman, Marie L. Lindegaard, Daniél Vega Møller, Sanjiv J. Shah, Marianne Bach Treppendahl, Subodh Verma, Mark C. Petrie
Journal: JACC Heart Failure (2023)

The majority of patients with heart failure with preserved ejection fraction (HFpEF) have the obesity phenotype, but no therapies specifically targeting obesity in HFpEF exist.The aim of this study was to describe the design and baseline characteristics of 2 trials of semaglutide, a glucagon-like peptide-1 receptor agonist, in patients with the obesity HFpEF phenotype: STEP-HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF; NCT04788511) and STEP-HFpEF DM (Semaglutide Treatment Effect in People with obesity and HFpEF and type 2 diabetes; NCT04916470).Both STEP-HFpEF and STEP-HFpEF DM are international multicenter, double-blind, placebo-controlled trials that randomized adults with HFpEF and a body mass index ≥30 kg/m2 to once-weekly semaglutide at a dose of 2.4 mg or placebo. Participants were eligible if they had a left ventricular ejection fraction (LVEF) ≥45%; NYHA functional class II to IV; a Kansas City Cardiomyopathy Questionnaire (KCCQ)-Clinical Summary Score (CSS) <90 points; and ≥1 of the following: elevated filling pressures, elevated natriuretic peptides plus structural echocardiographic abnormalities, recent heart failure hospitalization plus ongoing diuretic use, and/or structural abnormalities. The dual primary endpoints are the 52-week change in the KCCQ-CSS and body weight.In STEP-HFpEF and STEP-HFpEF DM (N = 529 and N = 617, respectively), nearly half were women, and most had severe obesity (median body mass index of 37 kg/m2) with typical features of HFpEF (median LVEF of 57%, frequent comorbidities, and elevated natriuretic peptides). Most participants received diuretic agents and renin-angiotensin blockers at baseline, and approximately one-third were on mineralocorticoid receptor antagonists. Sodium-glucose cotransporter-2 inhibitor use was rare in STEP-HFpEF but not in STEP HFpEF DM (32%). Patients in both trials had marked symptomatic and functional impairments (KCCQ-CSS ∼59 points, 6-minute walking distance ∼300 m).In total, STEP-HFpEF program randomized 1,146 participants with the obesity phenotype of HFpEF and will determine whether semaglutide improves symptoms, physical limitations, and exercise function in addition to weight loss in this vulnerable group.
Angiotensin-Neprilysin Inhibition in Patients With Mildly Reduced or Preserved Ejection Fraction and Worsening Heart Failure
Authors: Robert J. Mentz, Jonathan H. Ward, Adrian F. Hernandez, Serge Lepage, David A. Morrow, Samiha Sarwat, Kavita Sharma, Randall C. Starling, Eric J. Velazquez, Kristin M. Williamson, Akshay S. Desai, Shelley Zieroth, Scott D. Solomon, Eugene Braunwald
Journal: Journal of the American College of Cardiology (2023)

U.S. guidelines recommend consideration of sacubitril/valsartan in chronic heart failure (HF) and mildly reduced or preserved ejection fraction (EF). Whether initiation is safe and effective in EF >40% after a worsening heart failure (WHF) event is unknown. PARAGLIDE-HF (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF) assessed sacubitril/valsartan vs valsartan in EF >40% following a recent WHF event. PARAGLIDE-HF is a double-blind, randomized controlled trial of sacubitril/valsartan vs valsartan in patients with EF >40% enrolled within 30 days of a WHF event. The primary endpoint was time-averaged proportional change in amino terminal pro–B-type natriuretic peptide (NT-proBNP) from baseline through Weeks 4 and 8. A secondary hierarchical outcome (win ratio) consisted of: 1) cardiovascular death; 2) HF hospitalizations; 3) urgent HF visits; and 4) change in NT-proBNP. In 466 patients (233 sacubitril/valsartan; 233 valsartan), time-averaged reduction in the NT-proBNP was greater with sacubitril/valsartan (ratio of change: 0.85; 95% CI: 0.73-0.999; P = 0.049). The hierarchical outcome favored sacubitril/valsartan but was not significant (unmatched win ratio: 1.19; 95% CI: 0.93-1.52; P = 0.16). Sacubitril/valsartan reduced worsening renal function (OR: 0.61; 95% CI: 0.40-0.93) but increased symptomatic hypotension (OR: 1.73; 95% CI: 1.09-2.76). There was evidence of a larger treatment effect in the subgroup with EF ≤60% for NT-proBNP change (0.78; 95% CI: 0.61-0.98) and the hierarchical outcome (win ratio: 1.46; 95% CI: 1.09-1.95). Among patients with EF >40% stabilized after WHF, sacubitril/valsartan led to greater reduction in plasma NT-proBNP levels and was associated with clinical benefit compared with valsartan alone, despite more symptomatic hypotension. (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF; NCT03988634)
Polyphyllin D punctures hypertrophic lysosomes to reverse drug resistance of hepatocellular carcinoma by targeting acid sphingomyelinase
Authors: Yang Wang, Yan-Yan Chen, Gui-Bin Gao, Yang-Han Zheng, Nan-Nan Yu, Lan Ouyang, Xuejuan Gao, Nan Li, Shi-Yuan Wen, Shangjia Huang, Qian Zhao, Langxia Liu, Mingrong Cao, Shuixing Zhang, Jing Zhang, Qing-Yu He
Journal: Molecular Therapy (2023)

Hypertrophic lysosomes are critical for tumor progression and drug resistance; however, effective and specific lysosome-targeting compounds for cancer therapy are lacking. Here we conducted a lysosomotropic pharmacophore-based in silico screen in a natural product library (2,212 compounds), and identified polyphyllin D (PD) as a novel lysosome-targeted compound. PD treatment was found to cause lysosomal damage, as evidenced by the blockade of autophagic flux, loss of lysophagy, and the release of lysosomal contents, thus exhibiting anticancer effects on hepatocellular carcinoma (HCC) cell both in vitro and in vivo. Closer mechanistic examination revealed that PD suppressed the activity of acid sphingomyelinase (SMPD1), a lysosomal phosphodieserase that catalyzes the hydrolysis of sphingomyelin to produce ceramide and phosphocholine, by directly occupying its surface groove, with Trp148 in SMPD1 acting as a major binding residue; this suppression of SMPD1 activity irreversibly triggers lysosomal injury and initiates lysosome-dependent cell death. Furthermore, PD-enhanced lysosomal membrane permeabilization to release sorafenib, augmenting the anticancer effect of sorafenib both in vivo and in vitro. Overall, our study suggests that PD can potentially be further developed as a novel autophagy inhibitor, and a combination of PD with classical chemotherapeutic anticancer drugs could represent a novel therapeutic strategy for HCC intervention.
Interleukin-21 promotes Type-1 activation and cytotoxicity of CD56dimCD16bright natural killer cells during kidney allograft antibody–mediated rejection showing a new link between adaptive and innate humoral allo-immunity
Authors: Elodie Bailly, Camila Macedo, Jason Ossart, Kevin Louis, Xinyan Gu, Bala Ramaswami, Carol Bentlejewski, Adriana Zeevi, Parmjeet Randhawa, Carmen Lefaucheur, Diana Metes
Journal: Kidney International (2023)
Corrugated surface microparticles with chitosan and levofloxacin for improved aerodynamic performance
Authors: Chang-Soo Han, Ji-Hyun Kang, Eun hye Park, Hyo-Jung Lee, So-Jeong Jeong, Dong-Wook Kim, Chun-Woong Park
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Corrugated surface microparticles comprising levofloxacin (LEV), chitosan and organic acid were prepared using the 3-combo spray drying method. The amount and the boiling point of the organic acid affected the degree of roughness. In this study, we tried to improve the aerodynamic performance and increase aerosolization by corrugated surface microparticle for lung drug delivery efficiency as dry powder inhaler. HMP175 L20 prepared with 175 mmol propionic acid solution was corrugated more than HMF175 L20 prepared with 175 mmol formic acid solution. The ACI and PIV results showed a significant increase in aerodynamic performance of corrugated microparticles. The FPF value of HMP175 L20 was 41.3% ± 3.9% compared with 25.6% ± 7.7% of HMF175 L20. Corrugated microparticles also showed better aerosolization, decreased x-axial velocity, and variable angle. Rapid dissolution of drug formulations was observed in vivo. Low doses administered to the lungs achieved higher LEV concentrations in the lung fluid than high doses administered orally. Surface modification in the polymer-based formulation was achieved by controlling the evaporation rate and improving the inhalation efficiency of DPIs.
MUTE: A multilevel-stimulated denoising strategy for single cataractous retinal image dehazing
Authors: Shuhe Zhang, Ashwin Mohan, Carroll A.B. Webers, Tos T.J.M. Berendschot
Journal: Medical Image Analysis (2023)

In this research, we studied the duality between cataractous retinal image dehazing and image denoising and proposed that the dehazing task for cataractous retinal images can be achieved with the combination of image denoising and sigmoid function. To do so, we introduce the double-pass fundus reflection model in the YPbPr color space and developed a multilevel stimulated denoising strategy termed MUTE. The transmission matrix of the cataract layer is expressed as the superposition of denoised raw images of different levels weighted by pixel-wise sigmoid functions. We further designed an intensity-based cost function that can guide the updating of the model parameters. They are updated by gradient descent with adaptive momentum estimation, which gives us the final refined transmission matrix of the cataract layer. We tested our methods on cataract retinal images from both public and proprietary databases, and we compared the performance of our method with other state-of-the-art enhancement methods. Both visual assessments and objective assessments show the superiority of the proposed method. We further demonstrated three potential applications including blood vessel segmentation, retinal image registrations, and diagnosing with enhanced images that may largely benefit from our proposed methods.
Conversations on Goals of Care With Hospitalized, Seriously Ill Patients
Authors: Douglas B. White, Sarah K. Andersen
Journal: JAMA (2023)

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